Robert D Inman1, Basil Chiu. 1. Toronto Western Research Institute, University of Toronto, Toronto, Ontario, Canada. Robert.inman@uhn.on.ca
Abstract
OBJECTIVE: Although Chlamydia trachomatis-induced arthritis is among the most common rheumatic diseases having an identified infectious trigger, the pathogenesis of this arthritis is not well defined. We sought to investigate the host-microbe interactions that contribute to the severity of arthritis initiated by chlamydial infection. METHODS: We established an experimental rat model of C. trachomatis-induced arthritis that recapitulates many pathologic features of the clinical disease. The severity of the arthritis was defined using an established histopathologic scoring system. Host clearance of the pathogen and local cytokine production were examined by enzyme-linked immunosorbent assays. RESULTS: Lewis rats were susceptible to C. trachomatis-induced arthritis, whereas BN rats were relatively resistant to this disease. Significant differences in the histopathologic severity of arthritis were originally observed on day 21, and this prompted an examination of the acute phase of the arthritis. As early as day 5 after the onset of the arthritis, pathologic changes in Lewis rats were more severe than those in BN rats. An evaluation of the role of complement using cobra venom factor treatment excluded complement as being the key to differential sensitivity, because decomplementation did not eliminate the differences in arthritis severity between Lewis and BN rats. Host clearance, in contrast, was significantly different between the rat strains, with BN rats showing more prompt and effective clearance of the pathogen from both synovial tissues and spleen compared with Lewis rats. Local cytokine profiles demonstrated that host resistance was characterized by enhanced synovial expression of tumor necrosis factor alpha, interferon-gamma (IFNgamma), and interleukin-4. CONCLUSION: These studies demonstrated that cytokines thought to be proinflammatory in nature can play an important role in host defense in infection-triggered arthritis and serve to highlight the dynamic cytokine relationships that constitute effective host-pathogen interactions.
OBJECTIVE: Although Chlamydia trachomatis-induced arthritis is among the most common rheumatic diseases having an identified infectious trigger, the pathogenesis of this arthritis is not well defined. We sought to investigate the host-microbe interactions that contribute to the severity of arthritis initiated by chlamydial infection. METHODS: We established an experimental rat model of C. trachomatis-induced arthritis that recapitulates many pathologic features of the clinical disease. The severity of the arthritis was defined using an established histopathologic scoring system. Host clearance of the pathogen and local cytokine production were examined by enzyme-linked immunosorbent assays. RESULTS: Lewis rats were susceptible to C. trachomatis-induced arthritis, whereas BN rats were relatively resistant to this disease. Significant differences in the histopathologic severity of arthritis were originally observed on day 21, and this prompted an examination of the acute phase of the arthritis. As early as day 5 after the onset of the arthritis, pathologic changes in Lewis rats were more severe than those in BN rats. An evaluation of the role of complement using cobra venom factor treatment excluded complement as being the key to differential sensitivity, because decomplementation did not eliminate the differences in arthritis severity between Lewis and BN rats. Host clearance, in contrast, was significantly different between the rat strains, with BN rats showing more prompt and effective clearance of the pathogen from both synovial tissues and spleen compared with Lewis rats. Local cytokine profiles demonstrated that host resistance was characterized by enhanced synovial expression of tumor necrosis factor alpha, interferon-gamma (IFNgamma), and interleukin-4. CONCLUSION: These studies demonstrated that cytokines thought to be proinflammatory in nature can play an important role in host defense in infection-triggered arthritis and serve to highlight the dynamic cytokine relationships that constitute effective host-pathogen interactions.